PIK3CA mutation in gastric cancer and the role of microsatellite instability status in mutations of exons 9 and 20 of the PIK3CA gene

Abstract

A better understanding of molecular gastric cancer (GC) entities may help in tailored treatments of that neoplasm. The PIK3CA mutation is one of the most important in many cancers. We performed a comparison of clinical and pathological data of the PIK3CA mutation in GC patients. The analysis was done on 472 patients operated on in 1 center. Polymerase chain reaction (PCR) was used for the screening of PIK3CA (exon 9 and 20). For microsatellite instability (MSI) we used 5 quasi-monomorphic mononucleotide repeats - BAT-26, BAT-25, NR-24, NR-21, and NR-27. The clinical and pathological data was analyzed. PIK3CA mutation was observed in 10 out of 472 GC patients (2.1%). Nine out of 10 were MSI (9 of 111 MSI patients - 8.1%). Half of the 10 patients had mutations in exon 9 and the other half in exon 20. A majority of patients with the PIK3CA mutation had MSI (p < 0.001). The 5-year survival of MSI patients with the PIK3CA mutation was 40% and without the mutation, 70.4% (p = 0.309). For patients with the mutation in exon 9, the 5-year survival was 0%, and for those with the mutation in exon 20, 80% (p = 0.031). The Cox proportional hazards regression analysis did not show that PIK3CA is statistically correlated with a worse overall survival. PIK3CA mutation in GC is a rare finding. It is strongly associated with the MSI molecular subgroup, presenting a worse outcome than other MSI patients. A completely different outcome is associated with the mutation in exon 9 compared to the mutation in exon 20, with the latter being more favorable.